HIV-associated tuberculosis is the greatest public health challenge facing South Africa and many other countries in Africa. Over 6 million people are HIV infected in SA. HIV has driven a resurgence of TB and incidence rates approach 1% per annum. HIV co-infection is present in over 50% of TB cases giving rise to specific challenges in prevention, diagnosis and treatment. HIV-associated TB is the most common cause of death in SA. The University of Cape Town (UCT) is a global leader in HIV-associated TB with over 20 years experience of research and training. Particular strengths in the following areas exist: clinical trials (including treatment of TB-IRIS, the role of isoniazid preventive therpy in patients on ART, and trials of novel TB vaccines in HIV-infected individuals); the pharmacokinetics of ART and TB drugs, and pharmacokinetic- pharmacodynamic relationships of TB drugs; TB diagnostics in patients with HIV co-infection; the immune response to TB in HIV-infected patients; the pathogenesis of TB-IRIS; the immunology and diagnosis of latent TB in HIV-infected patients; and the impact of ART on the epidemiology of HIV-associated TB. Strong and productive relationships exist with the partnering institutions on this application (Johns Hopkins, University of North Carolina and Vanderbilt) in HIV-associated TB research and training. There are many unanswered and emerging research questions in the HIV-associated TB field, as drug resistance in both pathogens increases and treatment programs evolve. The next generation of researchers at UCT needs to be developed. In addition, we have identified several under-developed areas in our HIV-associated TB research platform that if addressed will lift our research to a higher level. Areas include mathematical modelling, advanced biostatistical capacity focussed on HIV-associated TB, bioinformatics skills for analysis of whole genome sequence and pharmacogenomics data and operational research. A 2 year planning process is proposed that will allow UCT with the 3 partner institutions to systematically document current HIV-associated TB research and training at UCT, define training needs and identify training programs and opportunities to meet these needs as well as synergies with existing training programs. A report of this process will be written and 2 symposia will be held that include partnering institutions. A D43 Fogarty Training Program grant application will be submitted. The envisaged training program will be focussed on PhD/post-doctoral fellowships awarded to high achieving early career researchers through competitive application processes. These fellowships will be co-supervised by faculty members at UCT and partnering US institutions in areas that specifically address UCT's research gaps. Fellows will spend defined periods of time in the US receiving training in skills and methodologies where this is not possible at UCT. Training courses in grant/manuscript writing and operational research and distance learning programs will also be included. We will identify 2 or 3 partnering universities in Africa with the goal of addressing their HIV-associated TB training needs in the form of joint training with UCT and home institutions. 1